Low-dose, low-dose-rate proton radiation modulates CD4+ T cell gene expression

Abstract

Purpose: To evaluate cluster of differentiation 4+ (CD4+) T cell gene expression and related parameters after whole-body exposure to proton radiation as it occurs in the spaceflight environment. Materials and methods: C57BL/6 mice were irradiated to total doses of 0, 0.01, 0.05, and 0.1 gray (Gy) at 0.1cGy/h. On day 0 spleens were harvested from a subset in the 0, 0.01 and 0.1Gy groups; (CD4+) T cells were isolated; and expression of 84 genes relevant to T helper (Th) cell function was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). Remaining mice were euthanized on days 0, 4, and 21 for additional analyses. Results: Genes with 2-fold difference and p0.05 compared to 0Gy were noted. After 0.01Gy, five genes were up-regulated (Ccr5, Cd40, Cebpb, Igsf6, Tnfsf4) and three were down-regulated (Il4ra, Mapk8, Nfkb1). After 0.1Gy there were nine up-regulated genes (Ccr4, Cd40, Cebpb, Cxcr3, Socs5, Stat4, Tbx21, Tnfrsf4, Tnfsf4); none were down-regulated. On day 0 after 0.01Gy, CD4+ T cell counts and CD4:CD8 ratio were low in the spleen (p0.05). Spontaneous DNA synthesis in both spleen and blood was lowest in the 0.01Gy group on day 0; on days 4 and 21 all p values were 0.1. Conclusion: The data show that the pattern of gene expression in CD4+ T cells after protracted low-dose proton irradiation was significantly modified and highly dependent upon total dose. The findings also suggest that low-dose radiation, especially 0.01Gy, may enhance CD4+ T cell responsiveness.